title: Effect of protein kinase Cbeta inhibition on renal hemodynamic function and urinary biomarkers in humans with type 1 diabetes: a pilot study.
abstract: OBJECTIVE
  The aim of this study was to examine the effect of protein kinase Cbeta inhibition with ruboxistaurin on renal hemodynamic function and urinary biomarkers (monocyte chemoattractant protein-1 [MCP-1] and epidermal growth factor) in renin angiotensin system blockade-treated type 1 diabetic subjects.
  
  
  METHODS
  Albuminuric subjects were randomized (2:1) to ruboxistaurin (32 mg daily; n = 13) or placebo (n = 7) for 8 weeks. Renal hemodynamic function was measured during clamped euglycemia or hyperglycemia and before and after ruboxistaurin or placebo.
  
  
  RESULTS
  Ruboxistaurin was not associated with between-group differences during clamped euglycemia or hyperglycemia. In a post hoc analysis comparing hyperfilterers with normofilterers during euglycemia, glomerular filtration rate and MCP-1 decreased, whereas the epidermal growth factor-to-MCP-1 ratio increased in hyperfilterers versus normofilterers (all P < 0.05).
  
  
  CONCLUSIONS
  The effect of ruboxistaurin is modest and dependent, at least in part, on the level of ambient glycemia and baseline glomerular filtration rate.
authors.affiliation: Division of Medicine, University Health Network, Toronto, Canada. david.cherney@utoronto.ca
authors.forename: David Z I
authors.initials: DZ
authors.lastname: Cherney
authors.forename: Ana
authors.initials: A
authors.lastname: Konvalinka
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.forename: Anton
authors.initials: A
authors.lastname: Soosaipillai
authors.forename: Heather
authors.initials: H
authors.lastname: Reich
authors.forename: Joanne
authors.initials: J
authors.lastname: Lorraine
authors.forename: Vesta
authors.initials: V
authors.lastname: Lai
authors.forename: James W
authors.initials: JW
authors.lastname: Scholey
authors.forename: Judith A
authors.initials: JA
authors.lastname: Miller
mesh_terms: D000419:Albuminuria / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects; D018932:Chemokine CCL2 / Q000187:drug effects / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000652:urine; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004815:Epidermal Growth Factor / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006439:Hemodynamics; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008301:Maleimides / Q000627:therapeutic use*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D064546:Protein Kinase C beta
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D004815:Epidermal Growth Factor; C099154:ruboxistaurin; D011493:Protein Kinase C; D064546:Protein Kinase C beta